Synthesis of Secondary Amines by Reduction of α-Amidoalkylphenyl Sulfones with Sodium Acetoxyborohydride

Abstract

α-Amidoalkylphenyl sulfones are stable precursors of reactive N-acylimines and can be fully reduced to the corresponding secondary amines using sodium acetoxyborohydride in dioxane at reflux.

Key words

amides - amines - imines - reductions - sulfones

References

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13

Typical Reduction Procedure: To a stirred suspension of NaBH₄ (10 mmol) in dry dioxane (10 mL), HOAc (10 mmol) was added dropwise in 10 min. After stirring for further 15 min, sulfone 7 (2 mmol) dissolved in dioxane (3 mL) was added and the white suspension was refluxed for 3 h. After cooling at r.t. the mixture was treated with H₂O (4 mL), extracted with CHCl₃ (4 × 10 mL) and the organic phase was dried over Na₂SO₄. After evaporation of the solvent the crude amine was purified by column chromatography. Alternatively the crude amine was dissolved in HCl sat. in MeOH to obtain the corresponding hydrochloride salt. MeOH was evaporated and the residue was taken up in dry Et₂O to precipitate the salt. After filtration, the salt was dissolved in 2 N NaOH (10 mL) and the free amine was extracted with CHCl₃ (4 × 10 mL). The organic phase was dried over Na₂SO₄ and the pure amine was recovered after evaporation of the solvent. Spectroscopic data for some representative compounds follows. Compound 4b: oil. IR (neat): 3255 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.83 (t, 3 H, J = 6.6 Hz), 1.10-1.57 (m, 12 H), 2.51-2.66 (m, 5 H), 2.85 (dt, 2 H, J = 47.6, 4.7 Hz), 4.90 (dt, 2 H, J = 28.2, 4.7 Hz). Compound 4h: oil. IR (neat): 3255 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.91 (t, 3 H, J = 7.0 Hz), 1.21-1.78 (m, 10 H), 2.54-2.66 (m, 5 H), 3.47 (t, 2 H, J = 6.2 Hz), 4.50 (s, 2 H), 7.18-7.38 (m, 5 H). Compound 4n: mp 52 °C. IR(nujol): 3300 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.88 (t, 6 H, J = 6.6 Hz), 1.11-1.61 (m, 32 H), 2.58 (t, 8 H, J = 6.6 Hz). Compound 7b: mp 58 °C. IR (nujol): 3300, 1660 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.87 (t, 3 H, J = 6.7 Hz), 1.21-1.52 (m, 10 H), 1.75-1.91 (m, 1 H), 2.22-2.38 (m, 1 H), 4.46 (dd, 1 H, J = 47.3, 14.6 Hz), 4.68 (dd, 1 H, J = 47.2, 14.6 Hz), 5.17 (dt, 1 H, J = 10.7, 3.1 Hz), 6.65 (d, 1 H, J = 8.5 Hz), 7.73-7.58 (m, 2 H), 7.63-7.69 (m, 1 H), 7.88-7.91 (m, 2 H). Compound 7n: mp 106 °C. IR (nujol): 3300, 1665 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.85 (t, 6 H, J = 6.6 Hz), 1.10-1.55 (m, 20 H), 1.60-1.91 (m, 4 H), 1.95-2.25 (m, 8 H), 5.26 (dt, 1 H, J = 10.6, 3.6 Hz), 4.68 (dd, 1 H, J = 47.2, 14.6 Hz), 5.17 (dt, 1 H, J = 10.7, 3.1 Hz), 6.50 (dd, 1 H, J = 10.6, 7.7 Hz), 7.50-7.71 (m, 3 H), 7.82-7.93 (m, 2H).